On the calculation of carbon and nutrient transport to the oceans.

Correct estimations of sediment, carbon, and nutrient fluxes are crucial for understanding the impacts of land use, environmental change, and climate change. However, limited measurements-often restricted to surface data or aliased data, i.e.

2025 European guideline on the management of infections.

Sexually transmitted infections remain common globally and most frequently are asymptomatic. The 2025 European guideline provides up-to-date guidance regarding indications for testing and treatment of infections. It includes advice on urogenital and extragenital testing including the use of self-collected specimens; recommendation to use only validated NAATs for diagnosis; and recommendation to treat all infections with doxycycline as first line in preference to single-dose azithromycin regimens.

Bacteriostatic and Immunomodulatory Effect of Xylocaine in the Context of Bladder Epithelial Cell Infection.

The application of urinary catheters is associated with pain and discomfort. Several topical medications are available to ease catheter insertion, including xylocaine. Here we report that xylocaine, although not classified as an antibacterial agent, has bacteriostatic properties against both Gram-positive and Gram-negative etiological agents of urinary tract infections (UTIs).

The Pharmacokinetic Interaction Between Metformin and the Natural Product Goldenseal Is Metformin Dose-Dependent: A Three-Arm Crossover Study in Adults With Type 2 Diabetes.

Pharmacokinetic drug interactions can lead to unexpected changes in plasma concentrations of the object drug, potentially increasing the risk for adverse effects and/or decreasing therapeutic efficacy. The botanical product goldenseal was previously shown to decrease metformin systemic exposure in healthy adults. This three-arm, open-label, crossover clinical study assessed the pharmacokinetic goldenseal-metformin interaction in adults with type 2 diabetes stabilized on therapeutic doses of metformin (500-2550 mg daily).

Lipid Packing Defects are Necessary and Sufficient for Membrane Binding of α-Synuclein.

α-Synuclein (αSyn), an intrinsically disordered protein implicated in Parkinson's disease, is potentially thought to initiate aggregation through binding to cellular membranes. Previous studies have suggested that anionic membrane charge is necessary for this binding. However, these studies largely focus on unmodified αSyn, while nearly all αSyn in the body is N-terminally acetylated (NTA).

Challenges of BTV-Group Specific Serology Testing: No One Test Fits All.

A newly formatted enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to bluetongue virus (BTV) was developed and validated for bovine and ovine sera and plasma. Validation of the new sandwich ELISA (sELISA) was achieved with 949 negative bovine and ovine sera from BTV endemic and non-endemic areas of Australia and 752 BTV positive (field and experimental) sera verified by VNT and/or PCR. The test diagnostic sensitivity (DSe) and diagnostic specificity (DSp) were 99.

Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.

Malaria remains a serious global health challenge, yet treatment and control programs are threatened by drug resistance. Dihydroorotate dehydrogenase (DHODH) was clinically validated as a target for treatment and prevention of malaria through human studies with DSM265, but currently no drugs against this target are in clinical use. We used structure-based computational tools including free energy perturbation (FEP+) to discover highly ligand efficient, potent, and selective pyrazole-based DHODH inhibitors through a scaffold hop from a pyrrole-based series.

Nonnegative matrix factorization for analyzing state dependent neuronal network dynamics in calcium recordings.

Calcium imaging allows recording from hundreds of neurons in vivo with the ability to resolve single cell activity. Evaluating and analyzing neuronal responses, while also considering all dimensions of the data set to make specific conclusions, is extremely difficult. Often, descriptive statistics are used to analyze these forms of data.

Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling.

Central tolerance of thymocytes to self-antigen depends on the medullary thymic epithelial cell (mTEC) transcription factor autoimmune regulator (Aire), which drives tissue-restricted antigen (TRA) gene expression. Vitamin D signaling regulates Aire and TRA expression in mTECs, providing a basis for links between vitamin D deficiency and autoimmunity. We find that mice lacking Cyp27b1, which cannot produce hormonally active vitamin D, display profoundly reduced thymic cellularity, with a reduced proportion of Aire mTECs, attenuated TRA expression, and poorly defined cortical-medullary boundaries.

Risk factors for Lyme disease among residents of rural, suburban, and urban areas in the United States: A Case-Control Study.

lyme disease (LD) is the most common vector-borne disease in the United States, with 476,000 cases estimated each year. It is unclear how LD risk factors vary by residential setting. We conducted a case-control study on LD risk by rural, urban, and suburban residential settings.

A QSPR Model for Henry's Law Constants of Organic Compounds in Water and Ethanol for Distilled Spirits.

Henry's law describes the vapor-liquid equilibrium for dilute gases dissolved in a liquid solvent phase. Descriptions of vapor-liquid equilibrium allow the design of improved separations in the food and beverage industry. The consumer experience of taste and odor are greatly affected by the liquid and vapor phase behavior of organic compounds.

Generation of tools for expression and purification of the phage-encoded Type I restriction enzyme inhibitor, Ocr.

DNA manipulation is an essential tool in molecular microbiology research that is dependent on the ability of bacteria to take up and preserve foreign DNA by horizontal gene transfer. This process can be significantly impaired by the activity of bacterial restriction modification systems; bacterial operons comprising paired enzymatic activities that protectively methylate host DNA, while cleaving incoming unmodified foreign DNA. Ocr is a phage-encoded protein that inhibits Type I restriction modification systems, the addition of which significantly improves bacterial transformation efficiency.

Bifunctionality and Antitumor Efficacy of ZG-126, a Vitamin D Receptor Agonist/Histone Deacetylase Inhibitor Hybrid Molecule.

Analogues of hormonal vitamin D, 1,25-dihydroxyvitamin D (1,25D), signal through the nuclear vitamin D receptor (VDR). They have potential in combination therapies with other anticancer agents such as histone deacetylase inhibitors (HDACi's). Here, we characterize the ZG series of hybrid compounds that combine HDACi within the backbone of a VDR agonist.

Using emergency department data to define a 'mental health presentation' - implications of different definitions on estimates of emergency department mental health workload.

Objective This study aimed to describe and compare the proportion of patients classified as an emergency department (ED) mental health presentation under different definitions, including the Australian Institute of Health and Welfare (AIHW) definition. Methods This retrospective cohort study enrolled all patients that presented to the EDs of a multi-centre Victorian health service between 1 January 2020 and 30 June 2023. Varying definitions of a mental health presentation were applied to each ED attendance, applying the current AIHW definition (using selected diagnosis codes), broader diagnosis-based coding, the presenting complaint recorded at triage and whether the patient was seen by or referred to the emergency psychiatric service (EPS).

An implantable piezoelectric ultrasound stimulator (ImPULS) for deep brain activation.

Precise neurostimulation can revolutionize therapies for neurological disorders. Electrode-based stimulation devices face challenges in achieving precise and consistent targeting due to the immune response and the limited penetration of electrical fields. Ultrasound can aid in energy propagation, but transcranial ultrasound stimulation in the deep brain has limited spatial resolution caused by bone and tissue scattering.

The natural history of isolated common femoral endarterectomy for chronic limb-threatening ischemia.

Objective: Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated common femoral endarterectomy (CFE) is highly effective. Because CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI).

Reasons for switching oral antipsychotic medications and related patterns of care and costs in patients with schizophrenia initiating monotherapy treatment: Claims-linked chart study.

Background: Antipsychotic switching is frequent in schizophrenia and is associated with poor clinical outcomes, increased health care resource utilization (HCRU), and increased health care costs. Research describing the reasons for antipsychotic switching in patients with schizophrenia and the associated impacts on HCRU and costs is limited.

Objective: To explore the reasons for oral antipsychotic medication (OAM) switching and describe HCRU and costs associated with OAM switching, stratified by reasons for switching, in patients with commercial or Medicare Advantage insurance in the United States.

Descriptive, Hospital-Based, 10-Year Study of Malaria Transmission in Goa, a Southwest Indian State in the Malaria Elimination Phase.

The South Asia International Center of Excellence for Malaria Research, an NIH-funded collaborative program, investigated the epidemiology of malaria in the Indian state of Goa through health facility-based data collected from the Goa Medical College and Hospital (GMC), the state's largest tertiary healthcare facility, between 2012 and 2021. Our study investigated region-specific spatial and temporal patterns of malaria transmission in Goa and the factors driving such patterns. Over the past decade, the number of malaria cases, inpatients, and deaths at the GMC decreased significantly after a peak in 2014-2015.